Biomedical subjects

M Kligerman

Publications and source records attributed to M Kligerman.

17 recordsLinked to original sources

PubMed1986

Protection by WR-2721 of human bone marrow function following irradiation.

Protection by WR-2721 of bone marrow (BM) from depression following hemibody irradiation (HBI) was assessed in patients receiving palliative therapy for widespread symptomatic metastasis on a Phase I/II Radiation Therapy Oncology Group (RTOG) protocol. Twenty-five patients are currently evaluable for the assessment of hematologic toxicity. HBI (600 or 700 cGy) was delivered starting 15-30 min after WR-2721 (600-900 mg/m2) intravenous infusion. Twenty patients from previous RTOG HBI studies were comparable in terms of radiation dose, hematologic data, and previous cytotoxic therapy. The WBC and platelet count nadirs at any time within 6 wk following HBI were used for data analysis, and toxicity was rated according to RTOG criteria. For the patients treated with WR-2721, moderate, severe, or life-threatening toxicity were seen in 16%, 12%, and 0% of the patients, respectively, compared to 30%, 15%, and 10% of patients in the group not treated with WR-2721. For the subpopulation of patients treated with the higher irradiation dose (700 cGy), differences in toxicity appeared to be greater. Conversely, for the sub-population of patients treated only to the upper hemibody, the difference in toxicity was less apparent. The percentage change from the median pre-treatment white blood cell (WBC) and platelet counts (PC) was not different between the WR-2721 treated and non-treated group; however, the median WBC count for the WR-2721 group returned to the pre-treatment value by the fourth week following HBI, whereas, it remained at 61% of the pre-HBI value for the control group. Within the group of patients treated with WR-2721, 5 of 17 (29%) receiving 600 mg/m2 demonstrated a greater than 75% decline in either WBC or platelets, compared to 0/8 patients treated with 750-900 mg/m2. These preliminary data support a protective effect by WR-2721 on radiation-induced bone marrow depression in humans, which may become more apparent with the use of higher radiation and WR-2721 doses.

Amifostine↗

PubMed1985

Increased MB-creatine kinase isoenzymes in an alcoholic population.

Using agarose gel electrophoresis MB-creatine kinase (MB-CK) activity was examined in the serum of 120 patients with acute alcohol intoxication admitted to a detoxification ward. Total CK activity was increased in 67 percent of patients and MB-CK activity was increased in 8.3 percent. Alcoholic patients also were studied by Sephadex chromatography and, in seven cases, MB-CK was greater than three standard deviations from the normal. Thus, this study demonstrates that acute alcohol intoxication is associated with increased MB-CK activity. These findings raise the possibility that excessive alcohol ingestion may lead to acute myocardial injury.

Adult↗

PubMed1984

Pulmonary hypertension, pulmonary edema, and decreased pulmonary compliance produced by increased ICP in cats.

Cats, anesthetized with sodium pentobarbital, were cannulated to measure pulmonary, systemic, and left atrial pressures and pulmonary ventilation, compliance, and resistance. Intracranial pressure was elevated to 30 mm Hg by injecting silicone oil into the extradural space. After an average time of 56 minutes, pulmonary systolic and diastolic pressures more than doubled, systemic systolic pressure sometimes rose and sometimes fell, and diastolic pressure rose 5%. Left atrial pressure never exceeded 8 cm of saline. Pulmonary compliance decreased by one-half, but airway resistance was unchanged. Pulmonary edema was estimated from histological sections. The pulmonary hypertension may be the result of a sympathetic discharge confined to the lung, since no remarkable changes in heart rate or systemic blood pressure occurred. The decrease in pulmonary compliance followed the rise in pulmonary arterial pressure, and is interpreted as the result of interstitial edema. There was no evidence that left heart failure or elevated left atrial pressure caused the pulmonary edema.

Animals↗

PubMed1982

Stereospecific chemoattraction of lymphoblastic cells by gradients of lysophosphatidylcholine.

Human plasma contains chemoattractant activity for cultured cells from the mouse thymic lymphoma 6C3HED and also for lymphoblasts from concanavalin A-stimulated mouse spleen cells. A major portion of the attractant activity for both cell types could be attributed to plasma lysophosphatidylcholine. Studies on synthetic lysophosphatides showed that polar head group structure, acyl chain length, and stereochemical configuration are important determinants for attractant activity.

Animals↗

PubMed1981

Early appearance of MB-creatine kinase activity in nontransmural myocardial infarction detected by a sensitive assay for the isoenzyme.

The early release patterns of MB-creatine kinase (CK-MB) in myocardial ischemia and infarction are largely unknown. We utilized a sensitive column chromatographic assay of CK-MB activity (precision = 1.1 IU/liter) and sequential CK-MB samples were obtained during the first 6 hours of illness to define the early time course of enzyme release. The average CK-MB in 39 normal subjects was 2.4 +/- 0.93 (mean +/- standard deviation (SD)). Twenty-two patients with ischemic chest pain, in whom myocardial infarction did not develop, were characterized by normal CK-MB's (2.4 +/- 1.0). Of 39 patients in whom transmural myocardial infarction developed, 28 (72 percent) were found to have abnormal CK-MB either initially or over a 20-minute sampling period. In contrast, 100 percent of the patients considered to have sustained a nontransmural myocardial infarction had abnormal initial CK-MBs and subsequently demonstrated significant increases in CK-MB from 28 +/- 19 initially to 41 +/- 30 IU/liter (P less than 0.01, N = 16) over the 20-minute sampling period. Thus, CK-MB appears earlier in plasma following nontransmural myocardial infarction than transmural myocardial infarction, probably reflecting perfusion to ischemic myocardium.

Chromatography, Ion Exchange↗

PubMed1979

Sensitivity and specificity of MB creatine kinase activity determined with column chromatography.

Several analytic techniques are used to estimate the activity of creatine kinase (CK) isoenzymes. These techniques are undergoing continual refinement because the MB CK molecule appears to be nearly cardiospecific. An improved column chromatographic assay is presented with a lower limit of analytic detection of 0.8 mlU/ml. The assay was applied to normal subjects and to patients with myocardial infarction and with complex disease states. Results of the column chromatography were compared with those of agarose and cellulose acetate electrophoresis. There was MB CK activity in all normal sera (no. = 19, mean +/- standard deviation = 2.4 +/- 7). After acute myocardial infarction the MB CK activity increased by 650 percent (no. = 86, mean +/- standard error of the mean = 158.2 +/- 12.6 mlU/ml). The sensitivity for myocardial infarction was 100 percent. The specificity, evaluated in multiple clinical states, approached 100 percent. The column assay was compared with both agarose and cellulose acetate electrophoresis, and poor correlations with these semiquantitative systems were demonstrated. Finally, peak MB CK activity was closely correlated with kinetic analyses used to estimate infarct size (r = 0.94). Thus, column chromatography is a sensitive and specific method of estimating MB creatine kinase activity and is more precise than current electrophoretic methods.

Acute Disease↗

PubMed1979

Gray-scale ultrasonography in the evaluation of neoplastic invasion of the base of the tongue.

Patients with primary carcinoma of the base of the tongue or direct invasion from contiguous areas were examined clinically and with ultrasound, and in some cases with computed tomography (CT), xerography, and polytomography. In all cases, multiple biopsy specimens were obtained. Utrasonography was better than the other imaging methods in delineating disease extent in the tongue itself, while CT and tomography were more useful in evaluating the retropharyngeal and lateral pharyngeal regions. It is suggested that ultrasound be used in the initial evaluation of such patients.

Aged↗

PubMed1975

Positive inotropic effects of methoxamine: evidence for alpha-adrenergic receptors in ventricular myocardium.

The present study was undertaken to evaluate the effects of methoxamine on force development and adenyl cyclase activity in cat ventricular myocardium. Methoxamine produced a dose-related increase in force development of isometrically contracting cat papillary muscles. The positive inotropic effects of methoxamine were not altered by beta-adrenergic blockade (propranolol), or catecholamine depletion by prior reserpinization, but were completely prevented by alpha-adrenergic blockade (phentolamine or ergotamine). Neither ergotamine, phentolamine, nor methoxamine had any direct effects on adenyl cyclase activity. Phentolamine did not attenuate the increase in force development produced by paired electrical stimulation, suggesting that it does not block the entry of calcium into the muscle. In summary, methoxamine produced a dose-related increase in force development of the cat papillary muscle that was selectively blocked by alpha-adrenergic receptors in ventricular myocardium.

Adenylyl Cyclases↗

PubMed1975

Myocardial and plasma levels of adenosine 3':5'-cyclic phosphate. Studies in experimental myocardial ischemia.

Alterations in myocardial and plasma levels of adenosine 3':5'-cyclic phosphate (cyclic AMP) were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic APM levels increased markedly after thoracotomy but returned to control levels two hours later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham-occlusion. After localized coronary occlusion, only modest and insignificant changes occurred in plasma cyclic AMP levels in anesthetized animals and also in conscious dogs. The present study suggests that adrenergically mediated changes in tissue cyclic AMP content are an early manifestation of both generalized and local myocardial ischemia, while the plasma cyclic AMP level is a relatively insensitive indicator of small coronary occlusions.

Animals↗

PubMed1975

Alterations in myocardial and plasma cyclic adenosine monophosphate in experimental myocardial ischemia.

Alterations in myocardial and plasma cyclic adenosine monophosphate (cyclic AMP) levels were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic AMP levels increased markedly after thoracotomy but returned to control levels 2 hr later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham occlusion. Localized coronary occlusion tended to increase plasma cAMP levels in anesthetized animals and also in concious dogs. The present study suggests that adrenergically mediated changes in tissue and plasma cyclic AMP content are early manifestations of both generalized and local myocardial ischemia and tend to reflect the magnitude of the insult.

Animals↗

PubMed1974